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dc.contributor.authorLandoni, Lauren Marie
dc.date.accessioned2018-01-05T19:26:43Z
dc.date.available2018-01-05T19:26:43Z
dc.identifier.urihttp://hdl.handle.net/10222/73558
dc.description.abstractAmyotrophic lateral sclerosis (ALS) causes progressive motor neuron (MN) degeneration leading to muscle weakness, paralysis, and eventually death. When symptoms are detected in ALS patients and model animals (SOD1G93A mice) large motor unit loss has occurred, indicating existence of a compensatory mechanism that masks denervation. Although significant denervation has occurred by P90 in SOD1G93A mice, motor disturbances are minimal. Cholinergic modulation of MNs through the C-boutons was hypothesized to compensate for motor unit loss by increasing the excitability of surviving MNs. After P100, V0C interneurons, the neuronal source of C-boutons, became active during walking in SOD1G93A mice and the ability to upregulate gastrocnemius activity during swimming became impaired. Silencing of the C-boutons in SOD1G93A mice caused earlier changes in gait and deficits in ankle range of motion. Based on these observations, targeting C-bouton activation using exercise or pharmacological therapies could improve quality of life in ALS patients by preserving mobility.en_US
dc.language.isoenen_US
dc.subjectAmyotrophic lateral sclerosisen_US
dc.subjectmotor neuron diseaseen_US
dc.subjectlocomotionen_US
dc.subjectcompensationen_US
dc.subjectc-boutonsen_US
dc.subjectcholinergic modulationen_US
dc.titleLocomotor Compensation for Severe Motor Neuron Loss during Amyotrophic Lateral Sclerosis Disease Progressionen_US
dc.date.defence2016-12-09
dc.contributor.departmentDepartment of Medical Neuroscienceen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.external-examinerDr. James Fawcetten_US
dc.contributor.graduate-coordinatorDr. Kazue Sembaen_US
dc.contributor.thesis-readerDr. Victor Rafuseen_US
dc.contributor.thesis-supervisorDr. Turgay Akayen_US
dc.contributor.ethics-approvalReceiveden_US
dc.contributor.manuscriptsNoen_US
dc.contributor.copyright-releaseNoen_US
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